| 1. |
- El-Huneidi, Waseem, et al.
(författare)
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Micromeria fruticosa Induces Cell Cycle Arrest and Apoptosis in Breast and Colorectal Cancer Cells
- 2020
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Ingår i: Pharmaceuticals. - : MDPI. - 1424-8247. ; 13:6
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Tidskriftsartikel (refereegranskat)abstract
- Micromeria fruticosa (L.) Druce subs p.serpyllifolia (Lamiaceae) has been used widely in folk medicine to alleviate various ailments such as abdominal pains, diarrhea, colds, eye infections, heart disorders and wounds. A few reports have confirmed different therapeutic potentialities of its extracts, including the anti-inflammatory, gastroprotective, analgesic, antiobesity and antidiabetic activities. This study aimed to investigate the mechanistic pathway of the antiproliferative activity of the ethanolic extract ofM. fruticosaon two different cancer cell lines, namely human breast (mammary carcinoma F7 (MCF-7)) and human colorectal (human colon tumor cells (HCT-116)) cell lines. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium (MTT) assay, Annexin V-FITC/PI, caspases 8/9 and cell cycle analyses, qRT-PCR and Western blot were used to assess the effect of M. fruticosaon cytotoxicity, apoptosis, cell cycle, cell cycle-related genes and protein expression profiles in MCF-7 and HCT-116. The extract inhibits cell proliferation in a time- and dose-dependent manner. The half-maximal inhibitory concentration (IC50) for both cell lines was found to be 100 mu g/mL. Apoptosis induction was confirmed by Annexin V-FITC/PI, that was related to caspases 8 and 9 activities induction. Furthermore, the cell cycle analysis revealed arrest at G2/M phase. The underlying mechanism involved in the G2/M arrest was found to be associated with the downregulation of CDK1, cyclin B1 and survivin that was confirmed by qRT-PCR and Western blotting.
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| 2. |
- Hernandez, Luiza I., et al.
(författare)
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Methods for evaluating cell-specific, cell-internalizing RNA aptamers
- 2013
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Ingår i: Pharmaceuticals. - : Multidisciplinary Digital Publishing Institute (M D P I AG). - 1424-8247. ; 6:3, s. 295-319
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Tidskriftsartikel (refereegranskat)abstract
- Recent clinical trials of small interfering RNAs (siRNAs) highlight the need for robust delivery technologies that will facilitate the successful application of these therapeutics to humans. Arguably, cell targeting by conjugation to cell-specific ligands provides a viable solution to this problem. Synthetic RNA ligands (aptamers) represent an emerging class of pharmaceuticals with great potential for targeted therapeutic applications. For targeted delivery of siRNAs with aptamers, the aptamer-siRNA conjugate must be taken up by cells and reach the cytoplasm. To this end, we have developed cell- based selection approaches to isolate aptamers that internalize upon binding to their cognate receptor on the cell surface. Here we describe methods to monitor for cellular uptake of aptamers. These include: (1) antibody amplification microscopy, (2) microplate- based fluorescence assay, (3) a quantitative and ultrasensitive internalization method (QUSIM) and (4) a way to monitor for cytoplasmic delivery using the ribosome inactivating protein-based (RNA-RIP) assay. Collectively, these methods provide a toolset that can expedite the development of aptamer ligands to target and deliver therapeutic siRNAs in vivo. © 2013 by the authors; licensee MDPI, Basel, Switzerland.
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| 3. |
- Källén, Bengt, et al.
(författare)
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The Use of Central Nervous System Active Drugs During Pregnancy
- 2013
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Ingår i: Pharmaceuticals. - : MDPI AG. - 1424-8247. ; 6:10, s. 1221-1286
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Forskningsöversikt (refereegranskat)abstract
- CNS-active drugs are used relatively often during pregnancy. Use during early pregnancy may increase the risk of a congenital malformation; use during the later part of pregnancy may be associated with preterm birth, intrauterine growth disturbances and neonatal morbidity. There is also a possibility that drug exposure can affect brain development with long-term neuropsychological harm as a result. This paper summarizes the literature on such drugs used during pregnancy: opioids, anticonvulsants, drugs used for Parkinson’s disease, neuroleptics, sedatives and hypnotics, antidepressants, psychostimulants, and some other CNS-active drugs. In addition to an overview of the literature, data from the Swedish Medical Birth Register (1996–2011) are presented. The exposure data are either based on midwife interviews towards the end of the first trimester or on linkage with a prescribed drug register. An association between malformations and maternal use of anticonvulsants and notably valproic acid is well known from the literature and also demonstrated in the present study. Some other associations between drug exposure and outcome were found.
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| 4. |
- Belal, Amany, et al.
(författare)
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A Novel Hydroxyapatite/Vitamin B-12 Nanoformula for Treatment of Bone Damage: Preparation, Characterization, and Anti-Arthritic, Anti-Inflammatory, and Antioxidant Activities in Chemically Induced Arthritic Rats
- 2023
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Ingår i: Pharmaceuticals. - : MDPI. - 1424-8247. ; 16:4
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Tidskriftsartikel (refereegranskat)abstract
- The usage of nanomaterials for rheumatoid arthritis (RA) treatment can improve bioavailability and enable selective targeting. The current study prepares and evaluates the in vivo biological effects of a novel hydroxyapatite/vitamin B-12 nanoformula in Complete Freunds adjuvant-induced arthritis in rats. The synthesized nanoformula was characterized using XRD, FTIR, BET analysis, HERTEM, SEM, particle size, and zeta potential. We synthesized pure HAP NPs with 71.01% loading weight percentages of Vit B12 and 49 mg/g loading capacity. Loading of vitamin B-12 on hydroxyapatite was modeled by Monte Carlo simulation. Anti-arthritic, anti-inflammatory, and antioxidant effects of the prepared nanoformula were assessed. Treated arthritic rats showed lower levels of RF and CRP, IL-1 beta, TNF-alpha, IL-17, and ADAMTS-5, but higher IL-4 and TIMP-3 levels. In addition, the prepared nanoformula increased GSH content and GST antioxidant activity while decreasing LPO levels. Furthermore, it reduced the expression of TGF-beta mRNA. Histopathological examinations revealed an improvement in joint injuries through the reduction of inflammatory cell infiltration, cartilage deterioration, and bone damage caused by Complete Freunds adjuvant. These findings indicate that the anti-arthritic, antioxidant, and anti-inflammatory properties of the prepared nanoformula could be useful for the development of new anti-arthritic treatments.
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| 5. |
- Belal, Amany, et al.
(författare)
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Therapeutic Potential of Zeolites/Vitamin B12 Nanocomposite on Complete Freunds Adjuvant-Induced Arthritis as a Bone Disorder: In Vivo Study and Bio-Molecular Investigations
- 2023
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Ingår i: Pharmaceuticals. - : MDPI. - 1424-8247. ; 16:2
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Tidskriftsartikel (refereegranskat)abstract
- Rheumatoid arthritis (RA) is a long-term autoimmune disease. As nanotechnology has advanced, a growing number of nanodrugs have been used in the treatment of RA due to their unique physical and chemical properties. The purpose of this study was to assess the therapeutic potential of a novel zeolite/vitamin B12 nanocomposite (Nano ZT/Vit B12) formulation in complete Freunds adjuvant (CFA)-induced arthritis. The newly synthesized Nano ZT/Vit B12 was fully characterized using various techniques such as XRD, FT-IR, BET analysis, HERTEM, SEM, practical size, zeta potential, XRF, and EDX. The anti-arthritic, anti-inflammatory, and antioxidant activities as well as the immunomodulation effect of Nano ZT/Vit B12 on the CFA rat model of arthritis were examined. Histopathologic ankle joint injuries caused by CFA intrapedal injection included synovium hyperplasia, inflammatory cell infiltration, and extensive cartilage deterioration. The arthritic rats Nano ZT/Vit B12 supplementation significantly improved these effects. Furthermore, in arthritic rats, Nano ZT/Vit B12 significantly reduced serum levels of RF and CRP, as well as the levels of IL-1 beta, TNF-alpha, IL-17, and ADAMTS-5, while increasing IL-4 and TIMP-3 levels. Nano-ZT/Vit B12 significantly declined the LPO level and increased antioxidant activities, such as GSH content and GST activity, in the arthritic rats. In arthritic rats, Nano ZT/Vit B12 also reduced TGF-beta mRNA gene expression and MMP-13 protein levels. Collectively, Nano ZT/Vit B12 seems to have anti-arthritic, anti-inflammatory, and antioxidant properties, making it a promising option for RA in the future.
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| 6. |
- Ström, Jakob O., 1983-, et al.
(författare)
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Hormesis and female sex hormones
- 2011
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Ingår i: Pharmaceuticals. - Basel, Switzerland : MDPIAG. - 1424-8247. ; 4:5, s. 726-740
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Forskningsöversikt (refereegranskat)abstract
- Hormone replacement after menopause has in recent years been the subject of intense scientific debate and public interest and has sparked intense research efforts into the biological effects of estrogens and progestagens. However, there are reasons to believe that the doses used and plasma concentrations produced in a large number of studies casts doubt on important aspects of their validity. The concept of hormesis states that a substance can have diametrically different effects depending on the concentration. Even though estrogens and progestagens have proven prone to this kind of dose-response relation in a multitude of studies, the phenomenon remains clearly underappreciated as exemplified by the fact that it is common practice to only use one hormone dose in animal experiments. If care is not taken to adjust the concentrations of estrogens and progestagens to relevant biological conditions, the significance of the results may be questionable. Our aim is to review examples of female sexual steroids demonstrating bidirectional dose-response relations and to discuss this in the perspective of hormesis. Some examples are highlighted in detail, including the effects on cerebral ischemia, inflammation, cardiovascular diseases and anxiety. Hopefully, better understanding of the hormesis phenomenon may result in improved future designs of studies of female sexual steroids.
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